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Title: | ELUCIDATION OF THE PATHOGENIC ROLE OF CD137 LIGAND IN A MURINE MODEL OF SYSTEMIC LUPUS ERYTHEMATOSUS | Authors: | ANSELM MAK | Keywords: | systemic lupus erythematosus, CD137 ligand, costimulation, T cells, interleukin-10, murine model | Issue Date: | 9-Mar-2017 | Citation: | ANSELM MAK (2017-03-09). ELUCIDATION OF THE PATHOGENIC ROLE OF CD137 LIGAND IN A MURINE MODEL OF SYSTEMIC LUPUS ERYTHEMATOSUS. ScholarBank@NUS Repository. | Abstract: | Systemic lupus erythematosus (SLE) is a complex autoimmune inflammatory condition. CD137 ligand (CD137L), via activating CD137 on T cells, is a potent driver of Tc/Th-1 responses. To investigate its involvement in the pathogenesis of SLE, B6.lpr-/-CD137L-/- double-knockout mice (DKO) were generated by crossing C57BL/6.Faslpr-/- (B6.lpr) lupus-prone mice and B6.CD137L-/- mice, which were compared phenotypically and immunologically, to B6.lpr and B6 WT mice. After a 22-month observation, DKO mice had significantly worse cutaneous lesions and glomerulonephritis, and higher mortality than their B6.lpr counterparts. DKO mice had a significantly higher proportion of Th17 cells than the B6.lpr mice. In vitro experiments revealed a significantly lower percentage of CD11b+ monocytes which were associated with lower intracellular IL-10 expression in the DKO than the B6.lpr mice. Additionally, DKO mice had significantly lower serum IL-10 levels than the B6.lpr mice. All these immunologic alterations are potentially responsible for more severe SLE after CD137L abrogation. | URI: | http://scholarbank.nus.edu.sg/handle/10635/138907 |
Appears in Collections: | Ph.D Theses (Open) |
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